Experimental anti-inflammatory brensocatib tolerated well in study
The therapy was recently approved as Brinsupri in the US for NCFBE
The experimental anti-inflammatory therapy brensocatib was generally well tolerated in adults with cystic fibrosis (CF), according to data from a small clinical trial aimed at aiding the design of future studies of the therapy.
Brensocatib’s pharmacological profile in CF patients is similar to its profile in people without CF, the findings also showed.
The study, “A Phase IIa, Single-Blind, Placebo-Controlled, Parallel-Group Study to Assess Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Brensocatib in Adults with Cystic Fibrosis,” was published in Clinical Pharmacokinetics. The work was funded by brensocatib’s developer Insmed.
CF is a genetic disease that causes thick mucus to build up in the lungs and other organs, impairing organ function and setting the stage for infections. Chronic lung inflammation is believed to play a major role in driving long-term lung problems for CF patients.
Brensocatib is an oral therapy that inhibits dipeptidyl peptidase (DPP1), a protein involved in inflammation. Brensocatib was recently approved as Brinsupri in the U.S. to treat non-cystic fibrosis bronchiectasis (NCFBE), a disorder marked by by lung inflammation similar to CF.
Since CF and NCFBE both show similar patterns of lung inflammation, and brensocatib has been shown to be beneficial in NCFBE, researchers believe it may also benefit CF patients. But CF can affect how drugs move through the body, resulting in pharmacologic profiles that are different from what are seen in other people. Therefore, before brensocatib’s efficacy in CF can be tested, its safety and pharmacological profile in CF patients must be evaluated first.
Testing different doses of Brensocatib
To do that, 29 adults with CF were randomly assigned to receive daily brensocatib at one of three doses (10, 25, or 40 mg), or a placebo, for 28 days in a Phase 2a clinical trial (NCT05090904) sponsored by Insmed.
The therapy was generally well tolerated, safety data showed. The most common issues reported were respiratory infections and headache, which have also been reported in people with NCFBE. The only serious safety issue was a lung infection that caused worsening CF respiratory symptoms, which happened in a patient given the highest dose.
“Brensocatib was generally well tolerated across the different doses, with no new safety signals reported,” the researchers wrote.
Pharmacological data were broadly consistent with what’s been seen in earlier studies of people with NCFBE and healthy volunteers. Most of the CF patients were taking CFTR modulators, which can improve the functionality of the protein whose defect or absence causes CF in people with certain disease-causing mutations. Brensocatib’s pharmacological profile wasn’t substantially altered when the drug was given alongside modulators.
These data indicate “the systemic exposure of brensocatib is not altered by highly effective CFTR modulators or by the disease status of CF,” wrote the researchers, who said their findings “support future clinical development of brensocatib for the treatment of CF.”
Brensocatib also tended to reduce inflammatory markers, indicating it seems to work as expected in CF patients. Additional studies will be needed to evaluate the its efficacy in CF, the researchers said.
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